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Use of human islets to understand islet biology and diabetes: progress, challenges and suggestions.

ABSTRACT: Over the last two decades, improved access to human islets and the development of human islet distribution networks have enabled the use of millions of human islets in hundreds of scientific research projects, leading to a dramatic increase in our understanding of human islet biology. Here we discuss recent scientific advances as well as methodological and experimental challenges that impact human islet quality, experimental outcomes and the reporting of human islets used in scientific publications. In a survey of over 200 scientific publications with human islet experimentation, we found that the reporting of critical information was quite variable, sometimes obscure, and often failed to adequately outline the experiments and results using human islets. As the complexity of human islet research grows, we propose that members of the human islet research ecosystem work together to develop procedures and approaches for accessible and transparent collecting and reporting of crucial human islet characteristics and, through this, enhance collaboration, reproducibility and rigour, leading to further advances in our understanding of human islet biology.

SUBMITTER: Hart NJ

PROVIDER: S-EPMC6325002 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Use of human islets to understand islet biology and diabetes: progress, challenges and suggestions.

Hart Nathaniel J NJ Powers Alvin C AC

Diabetologia 20181214 2

Over the last two decades, improved access to human islets and the development of human islet distribution networks have enabled the use of millions of human islets in hundreds of scientific research projects, leading to a dramatic increase in our understanding of human islet biology. Here we discuss recent scientific advances as well as methodological and experimental challenges that impact human islet quality, experimental outcomes and the reporting of human islets used in scientific publicati ...[more]

PMID: 30547228

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Project description:BackgroundCircular RNAs are non-coding RNA molecules with gene regulatory potential that have been associated with several human diseases. They are stable and present in the circulation, making them excellent candidates for biomarkers of disease. Despite their promise as biomarkers or future therapeutic targets, information on their expression and functionality in human pancreatic islets is a relatively unexplored subject.MethodsHere we aimed to produce an enriched circRNAome profile for human pancreatic islets by CircleSeq, and to explore the relationship between circRNA expression, diabetes status, genotype at T2D risk loci and measures of glycaemia (insulin secretory index; SI and HbA1c) in human islet preparations from healthy control donors and donors with type 2 diabetes using ANOVA or linear regression as appropriate. We also assessed the effect of elevated glucose, cytokine and lipid and hypoxia on circRNA expression in the human beta cell line EndoC-βH1.ResultsWe identified over 2600 circRNAs present in human islets. Of the five most abundant circRNAs in human islets, four (circCIRBP, circZKSCAN, circRPH3AL and circCAMSAP1) demonstrated marked associations with diabetes status. CircCIRBP demonstrated an association with insulin secretory index in isolated human islets and circCIRBP and circRPH3AL displayed altered expression with elevated fatty acid in treated EndoC-βH1 cells. CircCAMSAP1 was also noted to be associated with T2D status in human peripheral blood. No associations between circRNA expression and genotype at T2D risk loci were identified in our samples.ConclusionsOur data suggest that circRNAs are abundantly expressed in human islets, and that some are differentially regulated in the islets of donors with type 2 diabetes. Some islet circRNAs are also expressed in peripheral blood and the expression of one, circCAMSAP1, correlates with diabetes status. These findings highlight the potential of circRNAs as biomarkers for T2D.

Dataset Information

Use of human islets to understand islet biology and diabetes: progress, challenges and suggestions.

Publications

Use of human islets to understand islet biology and diabetes: progress, challenges and suggestions.

Similar Datasets

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